Human cytomegalovirus (CMV) is a virus of the herpesvirideae group and a species-specific β-herpesvirus that causes severe disease in neonates and in immunosuppressed individuals such as allograft transplant recipients and those with AIDS. In common with all herpesviruses, the life cycle of CMV is characterized by productive, latent and reactivation phases. During productive infection, viral genes are expressed in a temporarily regulated cascade resulting in the synthesis of new, infectious virus. At some point after initial infection, the virus establishes a life-long latent infection in myeloid lineage cells during which time viral gene expression is restricted and infectious virus is not produced. Periodically, virus can reactivate from latency, a process that results in the generation of infectious virus and which is the major cause of serious CMV associated diseases common in recipients of solid organ and bone marrow allografts. Other members of the herpesviridae group are also able to reactivate a latent state to cause clinical disease. The ability of CMV and other members of the herpesviridae family to persist in a latent state for the life of the host ensures a reservoir of virus for subsequent reactivation and highlights the importance of latency to the success of this virus as a human pathogen.
Attempts to understand the molecular basis of latency of viruses of the herpesvirideae group, such as CMV latency, have included studies to identify and characterize the function(s) of viral genes expressed during latent infection of myeloid progenitor cells. Studies utilizing cultured granulocyte-macrophage progenitors (GM-Ps) in an experimental model of latency identified two classes of CMV latency associated transcripts (CLTs), denoted sense and antisense CLTs, which originate from the major immediate early (MIE) region of the viral genome (3, 7-9, 19). However, the functions of the MIE region CLTs have not yet been defined. Furthermore, few studies have sought to assess viral gene expression during latency.
The present invention relates to the surprising discovery that a region of the genome of a virus of the herpesvirideae group is expressed during the latent phase of infection.